Welcome, everyone, to the 44th Annual J.P. Morgan Healthcare Conference. My name's Anupam Rama. I am one of the Senior Biotech Analysts here at J.P. Morgan. I'm joined by my squad: Ratih Pinhay, Priyanka Grover, Joyce Zhao. Our next presenting company is Solid Biosciences, and presenting on behalf of the company, we have CEO Bo Cumbo.
Yeah, thank you, Anupam. Thank you, J.P. Morgan, for the invitation. It's good to see all the friendly faces in the audience today, and those who are attending. Before I start, the forward-looking statements, I'll give you a pause on the forward-looking statements and tell you a little story. Before we actually started the presentation, I had two of our attorneys come up to me and talk about, "Are you excited about J.P. Morgan?" And I'm like, "Oh, great. What are you going to say?" "Well, I'm going to tell you about everything that's going on. We've dosed 33 patients, all safe, no drug-induced liver injury, no myocarditis, no aHUS. We've already enrolled our first patient and scheduled our first patient in the double-blind placebo control. We've dosed our first patient in FA. This is the best year that we've ever had as a company.
Our capsids—we've had 50 different agreements for our capsids. People are starting to come to us as a platform technology company and using all our delivery vehicles in Solid for next-generation therapies. We have TNNT2 that's on its way. We're getting ready to dose our first patient in CPVT. And I'm going to tell everyone around how we plan on taking the majority of the market share in our Duchenne space over time and how we believe that we're going to change patients' lives in FA." The two attorneys looked at themselves. They walked off, and the next thing you know, I get the note, cautionary note regarding forward-looking statements, so that's how we get this slide, and I've never seen a headline like that before, but you might want to read it because I'm going to say a lot of things, as you can tell.
I'm very pleased and happy to report, to show you this pipeline. Three years ago, when I was with Anupam, this was a vision, and when I was at this conference, we spoke on Thursday, and everything that you see on this slide was really a vision of what could become, but we actually had hopes and dreams, and we finally got here, and I do want to thank all our investors that really helped us with this journey over the last three years, and I think you can see now that we are poised, hopefully, to do great things for families and patients in the years to come. We have dosed, as I mentioned before, 33 patients in our phase 1/2 Duchenne trial called Inspire. We're about ready to dose our first patient in the double-blind placebo control trial.
He just screened negative for antibodies, which is a good thing, and he'll be enrolled very shortly or dosed very shortly in the next couple of months. We have dosed our first patient in Friedreich's ataxia, and this is a milestone that I want to screen from the rooftops. First ever time, first ever that anyone's dosed dual-route administration. You do an IV dosing for the heart and the spinal column. You do dentate nucleus dosing for the cerebellum. The patient is doing very well right now. It's early days. We have ways to go, but we're very pleased. We're close to, we had to prioritize. We're a little firm. We only have 119 employees and a small medical team. So we had to prioritize FA over CPVT. But we have over 30 patients that are trying to get into the trial for CPVT, three different sites.
And we should be dosing this quarter. We've now moved TNNT2 forward as well through GLP tox. And we're close to submitting an IND. I don't know if we can actually do it as a company because we're a little company, but this is another dilated cardiomyopathy. And then we have our capsid platform and our other programs. And I'll talk a little bit about that. Last year was an unbelievable year for execution of this company. We did things that Solid has never done before. And we dosed, as I mentioned, over 30 patients in our first trial. We had 30 different partnerships. I think it was right around 30 or 23 in Q1 of last year. And now we've exceeded over 50 different partnerships with our capsid program. FA, we received IND clearance at this time last year in this same meeting.
And now we've dosed our first patient. And CPVT, we had our IND last year as well. And now we're all poised for an unbelievable, potentially transformative year for Solid. For our capsid library, we just announced over 50 different partnerships. And I'll talk a little bit about that in the next couple of slides. For Duchenne, as I mentioned before, we're going to actually fully enrolled for our trial. If you look on ClinicalTrials.gov for the Inspire trial, we were planning on scheduling 50 to 60 patients in the study. As you know, we've dosed 33. However, we are fully enrolled. And we have more than enough patients for every single slot. And we're going to be notifying the sites, hopefully, in the next month or two, that we're basically not going to take any more recruitment because we filled every slot that's possible.
So now it's just about scheduling, doing the antibody test, scheduling, doing the biopsies, and getting them dosed. We are dosing our first patient in the double-blind placebo control trial. Our first patient will either be in Australia or Canada. We will also open up European sites. We believe they'll take about 18 months or so before we completely and fully enroll the double-blind placebo control trial. We're very excited about this trial because we want to bring this drug to every patient across the world. And we also plan on using this trial as a confirmatory study for accelerated approval in the United States. So it's critically important that we start dosing this trial soon. For FA, as I mentioned, we've already dosed our first patient. We've already got our second patient lined up. We have not scheduled him yet, but he's lined up.
We'll wait till we're cleared on safety from our first patient. We have a few more weeks to go. And then we'll start dosing the second patient and then ultimately third. And CPVT, as I mentioned before, we should be dosing this quarter. We'll talk a little bit about 003 and how we differentiate profile. And then we'll also talk about the capsid and sort of intertwine the two together. So we believe that 003 has significant potential and significant upside. It's compelling clinical profile demonstrated in the phase 1/2 trial. We've dosed 33 patients. In the patients that we've had microdystrophin, which are nine of 10, the mean expression is 58%. It's the highest of any of the microdystrophins that are out there to date. We're also at the lowest dose. And I think that's critically important when you think about it.
We're at 1E14. So we're a lower dose than all the drugs. You had a higher expression. We can show the dystrophin-associated protein complex at high levels. We actually quantify ourselves beta-sarcoglycan. So we can look at how well we're putting together the entire complex. And we have early cardiac data. Now, we look at cardiac data from a safety standpoint, but we're seeing observed troponin declines. And we're also seeing ejection fraction increases in patients that are low or low normal. Safety-wise, it's very well tolerated to date. And we do know that this is gene therapy that could change. But as we sit here today, we have 0% drug-induced liver injury. We have zero TMA, zero aHUS, zero myocarditis. And hopefully, that will continue. We're very humble in this space knowing that this is gene therapy and it can change.
To date, our safety profile looks very, very good. And that's in n of 33. And we'll talk a little bit about the potential significant commercial opportunity in a little bit. I think the landscape has changed dramatically of what the future will look like. And I think there's a major opportunity for this drug to have an impact in the market. Now, our program 003 leverages our next-generation technology to deliver this therapy. And what we use is a capsid called SLB101. This is the first time that this capsid has actually been in humans. The capsid is designed to bind to integrin receptors on skeletal and cardiac muscle. And that's why we get such enhanced and quick binding capacity and enhanced distribution, as well as liver de-targeting. We'll talk a little bit about this. The construct that's within the capsid is uniquely designed.
It contains R16 and R17 binding domain, which localizes nNOS to the muscle membrane, and nNOS is critically important, as you guys know, to help improve muscle perfusion. It increases blood flow, reduces pathology, fibrosis, and increases cardiac protection, and we believe that this is why we're seeing some of the benefits we are. We only use steroids, and that really separates us from the rest of the pack, and it's outpatient dosing, and so it's generally well tolerated, as mentioned before. Currently, we have not seen any drug-induced liver injury, TMA, aHUS, myocarditis. We use steroids alone. We also only use steroids for increased steroids for 30 days, and that is the shortest course of any of the companies that are in this gene therapy space.
From day 0 to day 30, we have an enhanced steroid regimen like the other companies do, but we taper at day 30. By day 60, all the patients, except for one, have been down to their standard steroid regimen. I think that's critically important. It also helps you when you look at day 90 responses. It makes you feel comfortable that those responses that you're seeing are not caused by steroids. They're actually caused by 003. I think that's important. We've talked a little bit about the expression. I think it is important to understand that we have the lowest viral load for the body. We're 1E14, 11 is the drug that's approved for Duchenne's 1.33E14. Then we have another therapy that's in clinical trials that's 2E14.
So when you think about the impact of the body from a viral load standpoint, we are the lowest. Now, what you're watching here is the footsteps of all the academics and all the small companies transition away from old-gen technology, the RH74, AAV9 capsids, AAV8 capsids, and move to the next-generation capsids. And I think this signals a wave that you should pay attention to because all the researchers are starting to realize that if you really want to change gene therapy and make gene therapy investable again, as well as hopefully get the clinical results, you need to change delivery. And delivery is critical. And we're seeing it in masses right now, 50-plus different groups we have agreements with. Some are academic labs. Some are small companies. Some are larger companies.
I think I am speaking to right now any investor that's out there that wants to invest in a small company, a gene therapy company, or a small gene therapy company or an academic. Don't use the old technology. There's a lot of really good technology that we have that will give you and will work with you to make sure that you can create next-generation programs so you can get money and investors into your platform. So if you are thinking about creating a new construct, call us. The email's at the bottom. And we'll make sure that we give you next-generation tools. By the way, it's not just our capsids. It's our dual plasmids companies are using our dual plasmids that helps increase our full-to-empty ratios. We have promoters across the board. We have buffers.
We can really help all the small companies and as well as the academic labs create better gene therapies for the future. And hopefully, we can make gene therapy really investable again. Now, what creates this new capsid that turns this into such a novel delivery mechanism is not just one-fold. And when you think about Formula 1 racing cars and you think about what makes a car so special, it's not just one; it's not the engine. It's not the airflow. It's not the driver. It's not the pit crew. It's all these pieces. And basically, that's what happened here with this capsid. You see two to three times better liver de-targeting in this capsid. Depending on the muscle, you can see anywhere from three to five times up to 10 times better distribution with this capsid.
It clears out of the blood within four days in humans, which is very different than AAV9, AAV8, etc. So it's already cleared. You can have a really high full-to-empty ratio. And it's all these little things that add up to turn this capsid into truly what's differentiated and turning this program into something special. But here's some of the data and the pre-clinical data I'll go through. And then we'll actually get into the clinical data. Whether you're looking at luciferase activity, you look at low doses in the mouse compared to AAV9 or RH74, there really is no comparison. And what is so shocking, and I think it translated so well, is the expression, the binding capacity, ultimately transduction and expression at day two and day four. Because we found out after the fact, once we dosed humans, that by day four, it's completely cleared.
So really, you're getting all this expression out of the first two days of this dosing. It matched exactly what we saw in the mouse. We also, when you compare it to AAV9 or RH74 and you look at the heart or the quadriceps, there is really no comparison when you look at the full change in luciferase. Hopefully, we're seeing that exactly play out in our program, our Duchenne program. We know it's liver de-targeting. We knew it was liver de-targeting the mice that's the top left-hand corner. What we saw in the monkeys down the bottom left was GGT levels. However, we didn't realize it was going to really translate that well into human. This is the liver biomarkers. It's like driving a flat road in the state of Florida. It's very clean. It's very flat.
There's not a lot of bumps. Your liver enzymes look like an EKG. It makes you feel really comfortable. And by the way, this is n of 14 because we're trying to keep the data clean and show you. But really, if I showed you n of 33, it's the exact same slide. All patients are doing very well. ALT, AST actually go down over time. GGT stays flat. Now, we made this slide, believe it or not, not for investors, not for the FDA. We've gathered all this data because when we first started doing the study, we were a $38 million company. We knew that there was competition on the way. We wanted to make sure that we felt that once you dose our therapy, that we had confidence internally to put the $100-plus million into the program and drive a program to the clinic.
What happened was it quite shocked us because we have 11 or 12 different measures here that all point in the same direction. It is almost impossible for you to argue that the drug is not doing something in the human body to shore up muscle. So we have different biomarkers here. Some are for the chronic phase, the acute phase of muscle integrity. Others are the chronic phase of muscle integrity. Others are for this muscle maturation when you think about embryonic myosin heavy chain. All of them point in the same direction. Many of them get stronger over time. It makes us feel really confident that our drug, 003, is doing something for these children. Long term, you're going to get that clinical benefit.
Now, our microdystrophin expression, it doesn't matter whether you look at Western Blot or Mass Spec, we have the highest expression that's out there. It's 58% for Western Blot, 58% for Mass Spec. For kids that have gone out longer, it's even higher expression. Immunofluorescence, which is positive fiber count, is roughly 51%-67% depending on the time. This is the highest in the industry. And we feel very confident that this long term is going to provide benefit for these kids. When you look at microdystrophin positive fibers and you do a comparison with either beta-sarcoglycan or nNOS positive fibers, you get a very positive response. And I believe that the Pearson correlation is 0.95% when you look at the two. And so we're the only company that's ever quantified beta-sarcoglycan, the actual DAPC, and did fiber count.
We're in the high 50s to 50-70% positive fiber count for beta-sarc. Then nNOS, the only company that can produce nNOS, which will obviously increase blood flow, decrease fibrosis, hopefully give cardiac benefit. We can produce this 26-36%. I want you to pause on this slide. Anyone who wants to talk about muscle pathology and whether this drug is actually doing something in the muscle needs to take a picture of this slide, go back and read what is embryonic myosin heavy chain. Because this is going to truly give you the confidence that this drug is doing something in the body and shoring up the muscle. After this presentation, I would hope someone would ask Dr. Brooks, who's our medical officer, why embryonic myosin heavy chain is so critically important. I'll give a quick overview.
I will tell you that when we showed this to our KOLs, one of them called him up the next day, Dr. Brooks, and said, "I couldn't sleep all night." Because this is a game changer. Muscle stem cells or satellite cells are activated to repair and replace damaged muscle fibers. In Duchenne, what you see is high levels of embryonic myosin heavy chain. You also ultimately deplete your satellite cell pool because of this. During this process, these newly formed dystrophic muscle fibers express embryonic myosin heavy chain. When you have a drug that creates microdystrophin and you're shoring up the muscle, if you're doing something, you should see a decline. We're seeing a decline of roughly 49%.
I believe that this is the one signal out of all our signals that should give everyone pause and say, "This drug is doing something to shore up muscle integrity," and ultimately, that's going to lead to clinical benefit for these boys. Whether we look at the chronic phase or the acute phase of muscle integrity, looking at serum CK, ALT, AST, titin, LDH, they all head in the right direction, whether it's day 90 or day 360, and keep in mind what I said earlier. At day 30, we start tapering our steroids, so by day 60, patients are already back down to where the kids started in Duchenne, so when you look at day 90, day 90 declines like this, you can feel very confident it's actually coming from the drug, not coming from steroids. We also measured troponin over time. Why do we measure troponin over time?
All these little boys in Duchenne, they have spikes in troponin. The physicians don't really do anything about it, but they're getting these little micro tears. Every two months or so, you'll see a spike in troponin in these little boys. Now, you'll have the naysayers say, "Well, you don't have cardiomyopathy at ages five, six, seven, eight." Correct. But they don't wake up overnight and just have cardiomyopathy at age 10, age 11, age 12. It starts early. And it starts with these little micro tears. And that's where you see these little spikes of troponin. So we've been measuring it over time. And what we're seeing is a decline of 70% of troponin. Now, we're also measuring this in our double-blind placebo control trial. Why? We're thinking about the future.
We're thinking about the time 10 years from now when we can show that we can change the structure of the heart. We can hopefully even change mortality and change the label. Because by measuring this from day one and tracking troponin and tracking ejection fraction, which we have here, we hope that we can show benefit and ultimately work this into the label. Ejection fraction is very unique. People will say, "At this age, you don't have low ejection fraction." That's not technically true. Duchenne is a very heterogeneous disease. You have a lot of kids that are, quote-unquote, "normal ejection fraction," right around 65. You have other kids that are in this low normal phase, one standard deviation below 65. And you have a few that are even further than that. And so we've been tracking all these boys and looking at ejection fraction.
And what's very interesting is if you were normal right around 65, you stay normal. If you're low normal, you go up. And if you're low, you go up as well. And that's what you see on the right-hand side. And we've been tracking this now for some patients over a year. And we're seeing the increases. And they're staying consistent. And this gives us a lot of hope for the future. For long-term mortality, we have to do the work. And we have to do the studies. And we're going to be tracking this in our double-blind placebo control trial. And we're going to be tracking those kids for five years. Now, our safety is actually getting better. And our thrombocytopenia is lower than it was. And it's because of how we tweaked and modified dosing of this capsid and this drug.
We feel really good about where the safety profile is. As I mentioned before, no drug-induced liver injury, no myocarditis, no aHUS, no TMA. The safety profile is actually getting better. The dosing has been intense. Some weeks we go, we've dosed five patients in one week. We actually didn't dose for the entire Christmas holidays. We stopped dosing right around December 10th, I think, December 11th. We did not dose Thanksgiving. You can see from November to basically January, we increased the number of participants a great deal. As I mentioned before, earlier in the presentation, ClinicalTrials.gov were scheduled to dose somewhere between 50 and 60 patients in this trial. We have filled every slot. So we are going to shut down recruitment pretty soon on this trial.
I feel terrible for the little boys that are trying to get in, but there's just too much demand for it. But we have the IMPACT Duchenne trial that's going to be opening up. That's going to be in Europe, Canada, and Australia. That's going to be our double-blind placebo control trial. My eyes are so bad, by the way. I contacted our head of IR. I said, "I think the fonts are wrong." She goes, "No, this is for Minecraft." And I was like, "Oh." So I had to quickly learn that this is Minecraft. And I thought my eyes were even getting worse. I don't even know what Minecraft is. Yeah. Well, we're trying to save kids. I don't understand them, but we're trying to save them. And I guess it's a game that they really like. But this trial is going to be active, and it's underway.
And I think it's real important for you to know that when we meet with the FDA later, either this quarter or early next, that we're going to already be dosing. And I think that's going to be important when we talk to the FDA that they know that we're not cutting corners, that we're actually trying to do what is right and give them a true double-blind placebo control confirmation study. Now, what are we going to do this year? We're going to have three meetings, hopefully by midyear with the FDA. The first one's already scheduled. That's the phase 3 placebo control discussion with the FDA. We have scheduled that. We've submitted the briefing book. We've not held the meeting. We don't have any minutes, obviously. But that's coming. And our second meeting will be somewhere late Q1 to mid-Q2.
There's about a three-month window there that we're aiming. That's going to be a very important meeting for us where we can start talking about external control benchmark data, publication benchmark data, our stat plan, and really get alignment with the FDA. I think it's real important for everyone to know that we have not looked at any of our functional data, zero functional data. So when you look at all our data, our patient data, you have safety data, you have the expression data, you have the blood work, the biological muscle integrity data, but then you have your functional data. That'll be like rise time, NSAA, stride velocity. None of that data has been reviewed. And why? Because when we actually talk to the FDA, we want to give them the confidence that we've not snooped the data.
When we're talking to them about external control, what external control to use, what publications to use, we have no idea what our data looks like. That'll give them confidence. They can even audit us. That'll give them a lot of confidence that when we set the stat plan, set the external control, set the publication review, now it can be no one snooped the data, and they can feel confident in that, and I think that's real important for you, and then later this year, we'll have a meeting to talk about the accelerated approval pathway and how much data you want. In U.K., there's a couple of things here, but we've got the ILAP, which is the Innovation Passport. I think that's very important for you to know that it's like Fast Track, Breakthrough, Orphan Drug, all wrapped up in one.
There's only three companies that receive this, and we're one of them. We could be U.K.'s first gene therapy to market. The opportunity is huge. The opportunity is huge. All right? And I won't take too much time to say other than to say, "I listened to our colleagues at Sarepta yesterday on how much they sold last quarter." And when I think about this, I think it's roughly about 40. My guess, without knowing, is roughly they sold about 40 patients' worth of therapy. Now, every single quarter in the United States, unfortunately, there's 100 boys born with this disease. So they are not even, my guess, not even close to 40%-50% of the actual birth rate per quarter. This market is actually getting bigger. There is a high need for new therapies, and hopefully, we can generate that.
Last two slides. I'm very proud to say we did the first-ever dual-route administration in Friedreich's ataxia. We use a capsid called HU68. It's a CNS-tropic capsid, because we need to get to the brain. We did a lot of work, and we know that you have to get to the cerebellum if you really want to make a difference. I want to tell you, I'm so proud to say that we really got to the cerebellum right where we wanted. Dr. Brooks can talk about the pinpoint accuracy of this. But we delivered our therapeutic right to the area. We were hoping to cover 15%-20% of the dentate nucleus. We blew away our internal target on delivery here. We're very pleased to know that the patient is doing well. The patient is resting at home.
It's too early to say all clear because we have a couple more weeks to do that. But right now, everything is good. We're going to dose three boys or three FA subjects, participants in the non-ambulatory phase. The first patient was in his late 20s. He was very severe from a CNS standpoint. If we actually see anything from this patient, it will be a miracle, and we will scream from the rooftops. But this is a safety study, and that is what it's designed to do. Once we go from non-ambulatory, we'll go to ambulatory, and then we'll work into even lower kids. This year could be transformational for us. We have a lot of different milestones to hit. We've got a lot of inflection points for investors, and we have a lot of data points or great studies for patients that are in need.
So with that said, I'll turn it over to questions. Thank you very much.
Thanks, Bo. So I'll ask the first couple of questions, and I'll open it up to the audience as well. So I guess my first question is, if you had to boil it down to where in the community in 2025, in the DMD community, there was a lot of talk about safety profile. And you presented 33 patients' worth of safety that looked very differentiated. Where is this differentiation coming from in terms of viral load or where is it?
Yeah. No, it's a great question. Actually, it goes back to the capsid. It goes back to my Formula One. It's not one thing that actually made it great. The capsid was liver de-targeting, and the preclinical models two to three-fold.
It was also better distribution depending on the muscle group, somewhere between three, five, six, seven-fold depending on the muscle group. We also knew that the purity was much better. So we were getting in the 75%-80% full-to-empty ratio. We knew the blood is clearing out of the blood at four days. And so it's out of the blood. And when you think about a complement activation or aHUS TMA and it's looking to clear the virus, it's not there. All of these little pieces, I believe, is what has turned this program into something that hopefully can be great one day. So I don't believe it's one smoking gun. I believe it's a lot of little pieces that made a big impact overall.
And then I think you're going to give us an actual SGT-003 data update. I think the slide said midyear. What's going to be the size and scope of that data? How much duration are we going to get? And kind of how do you think about not just on safety, but maybe differentiating on the expression and efficacy side?
Yeah. That's a great question. I'm going to hopefully hand over the question, but I'm going to turn it over to Dr. Brooks.
Yeah. So I think what Bo was sharing is that we shared before is that from a functional endpoint standpoint, this is all of the patient's data. We want to make sure that that contributes to the registration. And so we're holding that back as we shared. But this is, I think, an intensely rich data set that we'll be able to share as we proceed midyear with our discussions and alignment with the agency.
And then we know the street is really interested in understanding that, and we're thrilled to share that. We then that gives us the ability, I think, to then share all of the data in terms of what we can in terms of the biopsy data, the biomarker data, the progression of the biomarker data. And then there are also some really interesting data that we're looking at in terms of how these boys are doing functionally at home. So we actually are capturing that. It's very exciting data to look at and seeing how they're doing. And so we'll be excited to share that as well. So I think the cadence we talk to as it relates to our interactions and collaboration with the FDA. So that's that midyear time point.
And then the content, I think, is we want to share as much good news as we're seeing, which is the entirety of the data set minus what we need to safeguard, which is that registrational data point.
And then also, to your point on the midyear regulatory update, right? What are the series of scenarios that we should be thinking about based on the regulatory environment we are today in DMD?
Well, I mean, we're hopeful that we have a pathway for accelerated approval. And I think that we've done everything. I think we've done everything that we can to ensure that we have a good pathway. We've done. We're going to have a very large safety database, hopefully right around 50 patients in the next couple of quarters. We're going to start our double-blind placebo control trial.
We have not snooped any of the data, so we can actually have a great conversation with the FDA around external control as well as the stat plan, and I think the scenario will be we will have a path forward for accelerated approval sometime this year. And that means that we will, if that is the case, if we're fortunate enough to have those conversations and get that path, we should start a rolling BLA at the end of the year and finish up by mid-next year.
That is our game plan right now. We are also, as I mentioned, going to be enrolling in a double-blind placebo control trial ex-US. That'll take about 18 months to enroll, and our game plan is to use that trial for a confirmation study for the United States as well as full registrational approval ex-US, so I think those are the scenarios. Dr. Brooks?
Yeah. Absolutely. My CEO is very, very humble in the sense that I think that we are engaging with the agency and meeting them where they are. We want to be able we are in a position to show them we take seriously your guidance. And so we're holding safe this functional data. We are dedicated and have already started our double-blind randomized placebo control trial as part of your guidance. So when we come to them, we're coming to them from a position of we respect the guidance, we respect what you need to do to get to an approval. And I think that that means that I feel quite confident that that gives us every opportunity for a pathway for accelerated approval, and again, with news on that midyear this year.
Any final questions from the audience?